Efficacy and safety of adding gemtuzumab ozogamicin to conventional chemotherapy for adult acute myeloid leukemia: a systematic review and meta-analysis.

Introduction: Compared with the 3 + 7 regimen, the addition of gemtuzumab ozogamicin (GO) has improved survival in patients with acute myeloid leukemia (AML). We conducted a systematic review and meta-analysis to examine the overall efficacy and safety of GO in combination with conventional chemotherapy regimens in patients with AML.Methods: We searched several databases (MEDLINE, Embase, Web of Science and Cochrane Library). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS); odds ratios (ORs) with 95% CIs were calculated for the other outcomes.Results: Ten records involving 11 randomized controlled trials (RCTs) met the inclusion criteria. GO plus induction chemotherapy significantly increased RFS (HR: 0.84, 95% CI: 0.73-0.98), decreased the incidence of relapse (OR: 0.78, 95% CI: 0.68-0.91) and resistant disease (OR: 0.72, 95% CI: 0.61-0.84), and had no significant effect on the rate of complete remission (CR) with or without incomplete platelet recovery (OR: 1.21, 95% CI: 0.94-1.55), 30-day mortality (OR: 1.25, 95% CI: 0.99-1.57). Subgroup analysis showed significant OS benefits for patients with favorable cytogenetic (HR: 0.50, 95% CI: 0.28-0.89) or given GO at induction stage (HR: 0.91, 95% CI: 0.84-1.00). Compared with other dosing schedule groups, 3 mg/m2 fractionated schedule had a greater RFS benefit (HR: 0.52, 95% CI: 0.36-0.76) and lower relapse risk (OR: 0.48, 95% CI: 0.28-0.84).Conclusions: Adding low-dose GO to induction or both induction and post-remission chemotherapy has considerable efficacy and unequivocal safety for newly diagnosed adult AML.

MiR-429 prohibited NF-κB signalling to alleviate contrast-induced acute kidney injury via targeting PDCD4.

MiR-429 was reported to be downregulated in contrast-induced acute kidney injury (CI-AKI). However, whether miR-429 is functionally relevant with CI-AKI needs further investigation. Human renal tubular epithelial cell (HK-2) cells were stimulated with contrast media iodixanol to establish in vitro CI-AKI model. Cell Counting Kit-8 (CCK-8) was applied to access cell viability. Flow cytometry was performed to determine apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to evaluate level of programmed cell death 4 (PDCD4) mRNA and miR-429 while western blot was applied to evaluate level of proteins including PDCD4, B-cell leukaemia/lymphoma 2 (Bcl-2), BCL2-associated X protein (Bax), cleaved caspase 3, cleaved caspase 9, p65, phosphorylated p65. Dual luciferase assay was used to validate miR-429 targeting PDCD4. MiR-429 was downregulated whereas PDCD4 was upregulated in contrast media iodixanol-stimulated HK-2 cells. MiR-429 overexpression elevated cell viability and attenuated cell apoptosis. Moreover, the activation of nuclear factor kappa-B (NF-κB) signalling was suppressed after miR-429 overexpression, while PDCD4 overexpression reversed these effects. MiR-429 directly targeted PDCD4 and negatively regulated its expression. CI-AKI induced NF-κB signalling activation and PDCD4 overexpression further promoted NF-κB signalling activation. However, the treatment of BAY11-7082 reversed above results. Overexpression of miR-429 attenuated apoptosis and elevated cell viability in a CI-AKI cell model via targeting PDCD4 and thus restraining NF-κB signalling.

The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: a systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy and adverse effects of venetoclax(VEN) in combination with hypomethylating agents(HMAs) in acute myeloid leukemia(AML) or myelodysplastic syndrome(MDS). METHODS: Clinical studies were identified from the Cochrane Library, PubMed, Embase, Google Scholar, and ClinicalTrials.gov. Overall complete remission (CR) and overall response rate (ORR) were used to evaluate the efficacy of VEN in combination with HMAs for AML/MDS, the incidence of the 4 most common grade 3-4 adverse events was used to evaluate safety. RESULTS: We identified 13 studies that included a total of 1059 patients. 7 cohort studies and 5 non-randomized controlled trials(NRCTs) were analyzed by random-effects model, and subgroup analyses showed the pooled overall CR rate of 62% (95% CI 57-67%, I2 = 3%) for the new-diagnosed(ND) AML group, 39% (95% CI 30-48%, I2 = 28%) for relapsed/refractory(R/R)-AML, and 61% (95% CI 50-71%, I2 = 25%) for MDS, respectively. There was only one randomized controlled trial(RCT) that showed a CR rate of 66.4% in the patients who received azacitidine(AZA) plus VEN. A total of 8 studies reported adverse events, with cytopenia and infection being the most common grade 3-4 adverse events. CONCLUSIONS: The addition of VEN to HMAs may provide significant clinical benefit for AML/MDS patients, where response rates are better in MDS and ND-AML than in R/R-AML, but attention should be paid to the possible increased risk of febrile neutropenia.

Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats.

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-ß1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.

Leukaemia cutis as a specific skin involvement in chronic myelomonocytic leukaemia and review of the literature: Acknowledgments.

The skin involvement of myeloid leukaemia is conventionally divided into specific malignant lesions and non-specific benign lesions, and these categories are also applicable in chronic myelomonocytic leukaemia (CMML). According to the 2016 World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues, CMML is defined as a myeloid neoplasm with characteristics of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs). As a specific cutaneous sign of extramedullary infiltration, leukaemia cutis (LC) is a rare occurrence in patients with CMML, and only approximately 89 cases have been reported in the literature thus far. The clinical features of LC are varied, and LC in CMML exhibits heterogeneous histopathologic features, with manifestations as cutaneous nodules or papules that are composed of blast cells showing either granulocytic or monocytic differentiation. Skin biopsy and further immunohistochemical examination are essential at the time of diagnosis to evaluate pathological type and determine the clinical course. Generally, once diagnosed as LC in CMML, this unusual skin lesion might be an indicator of transformation to acute myeloid leukaemia (AML) and is associated with a poor prognosis. The main treatment is allogeneic stem cell transplantation (ASCT). Therefore, early diagnosis and accurate identification have important therapeutic and prognostic significance in CMML patients with skin infiltration.

Ophiopogonin D of Ophiopogon japonicus ameliorates renal function by suppressing oxidative stress and inflammatory response in streptozotocin-induced diabetic nephropathy rats

Ophiopogonin D (OP-D) is the principal pharmacologically active ingredient from Ophiopogon japonicas, which has been demonstrated to have numerous pharmacological activities. However, its protective effect against renal damage in streptozotocin (STZ)-induced diabetic nephropathy (DN) rats remains unclear. The present study was performed to investigate the protective effect of OP-D in the STZ-induced DN rat model. DN rats showed renal dysfunction, as evidenced by decreased serum albumin and creatinine clearance, along with increases in serum creatinine, blood urea nitrogen, TGF-β1, and kidney hypertrophy, and these were reversed by OP-D. In addition, STZ induced oxidative damage and inflammatory response in diabetic kidney tissue. These abnormalities were reversed by OP-D treatment. The findings obtained in the present study indicated that OP-D might possess the potential to be a therapeutic agent against DN via inhibiting renal inflammation and oxidative stress.

LncRNA PRINS is involved in the development of nephropathy in patients with diabetes via interaction with Smad7.

Long non-coding RNA psoriasis-susceptibilityrelated RNA gene induced by stress (PRINS) is known to be involved in kidney ischemia reperfusion injury. The aim of the current study was to investigate the potential role of PRINS in diabetic nephropathy. The relative mRNA expression level of PRINS and SMAD family member 7 (Smad7) was examined in patients with diabetes, including patients without obvious complications (n=43), patients with diabetic nephropathy (n=33), diabetic retinopathy (n=37), diabetic cardiomyopathy (n=29), diabetic lung disease (n=38) and healthy controls (n=48). Correlation analysis between the expression level of PRINS and Smad7 was analyzed by Pearson's correlation analysis. In addition, overexpression of PRINS was confirmed in mouse podocyte cells and cell viability and Smad7 protein expression was detected by MTT assay and western blot analysis, respectively. The expression levels of PRINS and Smad7 were significantly increased in patients with diabetes compared with healthy controls. In addition, the expression levels of PRINS and Smad7 were significantly increased in patients with diabetic nephropathy compared with other diabetic complications. The expression level of PRINS in mouse podocyte cells was upregulated following treatment with high glucose. A significant positive correlation between the expression level of PRINS and Smad7 was observed in patients with diabetic nephropathy. However, there was no correlation was observed in other patient groups compared with healthy controls. Overexpression of PRINS decreased the viability of mouse podocyte cells and enhanced Smad7 protein expression. Taken together, these results suggest that PRINS may be involved in the development of nephropathy in patients with diabetes.

Outcomes of 219 chronic myeloid leukaemia patients with additional chromosomal abnormalities and/or tyrosine kinase domain mutations.

INTRODUCTION: To confirm the role of additional chromosomal abnormalities (ACAs) and kinase domain (KD) mutations in the progression and outcomes of Chronic myeloid leukaemia (CML) patients and the connection between them, we analysed the ACAs and KD mutations of 219 CML patients admitted to our hospital. METHODS: Cytogenetic analysis of metaphases was performed to detect ACAs, and the BCR-ABL1 KD was sequenced to detect KD mutations. RESULTS: Twenty-four patients (11.0%) had ACAs in addition to the BCR-ABL1 or t(9;22)(q34;q11) translocation. The most common abnormality was trisomy 8. Twelve different KD mutations were observed in 13 out of 53 imatinib-resistant patients (24.5%). p.(Y235H) (n = 3; 23.07%), p.(F359V) and p.(T315I) (n = 2; 15.38%) presented most frequently. KD mutations subtypes (p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V)) coexisted with ACAs. The incidence of CML progression was 12/22 (54.5%) in the group of patients with ACAs and/or KD mutations and 2/143 (1.4%) in the group of patients without ACAs or KD mutations (CI 95%, P < 0.001) and was higher in the KD mutations group than in the ACAs group (P = 0.046). The group of patients with ACAs and/or KD mutations had more men than the group of patients without ACAs or KD mutations (P = 0.013). CONCLUSION: We conclude that ACAs and/or KD mutations are related to CML progression and are adverse outcome factors. Their presence exhibits gender differences and is more common in males. p.(E255K), p.(T315I), p.(F359V), p.(M244V) and p.(L298V) emerge more frequently when ACAs and KD mutations coexist.

Characterization of pediatric hospital-associated infection caused by methicillin-resistant Staphylococcus aureus in mainland China.

BACKGROUND: This study was conducted to investigate the clinical features of hospital-associated infections (HAIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) in Chinese children, and the molecular characteristics of the bacteria. METHODS: Patients with HAIs caused by MRSA were identified retrospectively. All isolates were analyzed using molecular typing and antimicrobial susceptibility tests. RESULTS: In total, 150 patients were identified, with a median age of 18 months. The most common infection was pneumonia (55.3%), followed by skin and soft tissue infections (46%). Invasive infections were observed in 52 patients (34.7%), and their hospital stay was longer compared with non-invasive cases (21 vs 12 days, p = 0.047). A total of 16 sequence types (STs) were identified. ST239 and ST59 were common clones, accounting for 46% and 28% of cases, respectively. Compared with cases caused by ST239-SCCmecI-III, patients infected by ST59-SCCmecIV-V had a lower median age (11 vs 41 months, p = 0.047) and more commonly developed invasive infection (50% vs 18.8%, p = 0.006). CONCLUSIONS: Invasive infections accounted for a large proportion of HAIs caused by MRSA. ST59-SCCmecIV/V, a common clone in the community, caused HAIs in Chinese children, more often infected younger children and caused invasive infections.

Clinical and molecular characteristics of community-acquired methicillin-resistant Staphylococcus aureus infections in Chinese neonates.

This study aims to characterize the clinical features of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in Chinese neonates, as well as the molecular characteristics and expression of key virulence genes of isolates. Clinical information and molecular characteristics of 130 cases were analyzed. Up to 83.8% patients were affected with late-onset infection. Cesarean delivery was the main delivery route, accounting for 74.6% of the total deliveries. Pneumonia (69, 53.1%) was the most common infection. A total of 38 patients (29.2%) suffered from complications. Moreover, 35 cases (26.9%) were invasive infections, among which 88.6% involved multiple organs and 45.7% suffered from complications. Cesarean section and premature birth were the risk factors for invasive CA-MRSA infection. ST59-MRSA-SCCmecIVa-t437 (54, 41.5%) was the most predominant CA-MRSA clone. The hla expression in the ST59 isolates was higher than that in ST910 (p = 0.02) and the hla expression in ST59-SCCmecV-t437 was higher than that in ST59-SCCmecIVa-t437. Approximately, 46.4% (13/28) of the infections caused by ST59-SCCmecV were invasive. This value is higher than that of ST59-SCCmecVa caused infections (14/59, 23.7%) (p = 0.03). This study showed that neonatal CA-MRSA infections in China readily become invasive, involve multiple organs, and are often accompanied by complications. The SCCmec V clone may be more pathogenic than the SCCmecVIa clone.

Clinical and molecular characteristics of invasive community-acquired Staphylococcus aureus infections in Chinese children.

BACKGROUND: This study aims to investigate the clinical features of invasive community-acquired Staphylococcus aureus (CA-SA) infection in Chinese children and analyze its molecular features. METHODS: Clinical data and invasive CA-SA isolates were prospectively collected. Pediatric risk of mortality (PRISM) score was used for disease severity measurement. Molecular typing was then performed, followed by expression analysis for virulence genes. RESULTS: Among 163 invasive CA-SA infection cases, 71 (43.6%) were methicillin-resistant SA (MRSA) infections and 92 (56.4%) were methicillin-susceptible SA (MSSA). A total of 105 (64.4%) children were younger than 1 year old, and 79.7% (129/163) were under 3 years age. Thirteen kinds of diseases were observed, in which bacteremia and pneumonia accounted for 65.6% (107/163) and 52.8% (86/163), respectively. A total of 112 (68.1%) patients had two or more infective sites simultaneously, and four cases (2.5%) died. CA-MSSA more frequently caused multi-sites infections, bacteremia, and musculoskeletal infection than MRSA. A total of 25 sequence types (STs) were detected. MRSA mainly comprised ST59 (49/71, 69%), whereas the most frequent clonotypes were ST88 (15/92, 16.3%), ST25 (13/92, 14.1%), ST7 (13/92, 14.1%), ST2155 (12/92, 13%), and ST188 (9/92, 9.8%) for MSSA. Seven STs were common to both MSSA and MRSA groups. No differences in clinical presentation or PRISM score were found between the two groups or among different ST. The expression levels of the four known virulence genes varied among the six main ST clones. CONCLUSIONS: Invasive CA-SA infections were characterized by high incidence and multi-site infections in young children in China. The clinical manifestations of CA-MSSA were more frequently associated with multi-site infections, bacteremia and musculoskeletal infection than those of CA-MRSA. Isolated genotypes may be relevant to the expressions of virulence genes, but not to clinical manifestations.

Prevalence and invasiveness of community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis.

BACKGROUND: Reports suggest that the prevalence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) has increased, and that CA-MRSA is more virulent than healthcare-associated (HA)-MRSA. AIMS: The aim of this study is to gain a better understanding of the invasiveness and prevalence of CA-MRSA in patients; we systematically reviewed the literature by conducting a meta-analysis. MATERIALS AND METHODS: We searched the MEDLINE and PUBMED databases from the year these databases were established to January 2013. RESULTS: The pooled CA-MRSA prevalence among 50,737 patients from 33 studies was 39.0% (range, 30.8-47.8%). The pooled CA-MRSA prevalence rates among pediatric and adult patients with MRSA infection were 50.2% (range, 37.5-62.8%) and 42.3% (range, 16.4-73.3%), respectively. The pooled CA-MRSA prevalence rates of MRSA-infected patients in Asia, Europe, and North America were 23.1% (range, 12.0-39.8%), 37.4% (range, 21.1-56.4%), and 47.4% (range, 35.8-59.4%), respectively. Using the random effects model, we determined that the pooled odds ratio of invasive infections in CA- and HA-MRSA was 0.30 (95% confidence interval: 0.08-1.10; P = 0.07, test for heterogeneity P < 0.00001). CONCLUSIONS: The prevalence of CA-MRSA in MRSA infection varied with area and population. No difference in the ability to cause invasive infections was found between CA- and HA-MRSA. This finding challenges the view that CA-MRSA is more virulent than HA-MRSA.

Comparative analysis of the virulence characteristics of epidemic methicillin-resistant Staphylococcus aureus (MRSA) strains isolated from Chinese children: ST59 MRSA highly expresses core gene-encoded toxin.

This study aims to investigate the prevalence of a novel cell wall-anchored protein gene, sasX, and to obtain information on the genetic basis for the pathogenic potential of the MRSA strains isolated from Chinese children. The molecular and virulence characteristics of the clinical strains were analyzed. Twenty-two sequence types (STs) were obtained, with six epidemic clones ST59, ST239, ST1, ST910, ST88, and ST338 accounting for 35.8, 22, 6.6, 6.6, 5.3, and 4.1% respectively. The expression levels of hla, psmα, and RNAIII were higher in ST59 than in other STs (p < 0.05). The sasX gene was detected in 26 (10.7%) MRSA isolates. ST239-MRSA-SCCmecIII-t037 (61.5%) was the predominant sasX-positive MRSA clone. The expressions of PSMα and RNAIII were higher in sasX-positive ST239 isolates than in sasX-negative ST239 ones (p < 0.01). Notably, the percentage of invasive infection in infections caused by sasX-positive ST239 MRSA was higher than that by sasX-negative ST239 MRSA (p = 0.008). This study indicated that ST59 was the predominant clone in the MRSA isolates obtained from Chinese children and might have stronger pathogenic potential. The prevalence of the sasX gene in the MRSA isolates from children was relatively low. Furthermore, the sasX gene might be related to the expressions of PSMα and RNAIII and infection invasiveness.

Hospital- and community-associated methicillin-resistant Staphylococcus aureus: a 6-year surveillance study of invasive infections in Chinese children.

AIM: To investigate and compare the characteristics of invasive hospital-associated (HA) and community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) infections in Chinese children. METHODS: Clinical data on 59 paediatric patients with invasive MRSA isolated from the normally sterile sites between 2006 and 2011 were obtained from the clinical MRSA surveillance database of Beijing Children's Hospital. The molecular characteristics of the invasive MRSA strains were then analysed. RESULTS: Invasive MRSA infections rose from 0.89 per 10 000 admissions in 2006 to 3.75 in 2011, with a notable increase in invasive CA-MRSA infections from 0 to 2.43 over the same period. The median age of the CA patients (n = 29) was 0.33 years, compared with 1.17 years for the HA patients (n = 30). Multisite infection, severe pneumonia and empyema were found in 55.2%, 73.1% and 61.5% of CA children and in 30%, 32% and 24% of HA patients, respectively. ST59-MRSA-IVa accounted for 40.7% of all isolates and the Panton-Valentine leukocidin (PVL) gene carriage rate was significantly higher in patients with necrotizing pneumonia and osteoarthritis than in those with other diseases. CONCLUSION: The incidence of paediatric invasive MRSA infection, particularly CA-MRSA infection, increased in Chinese children between 2006 and 2011. The invasive infections caused by CA-MRSA occurred more frequently in younger children with more severe pneumonia or empyema.

A C3-symmetric colorimetric anion sensor bearing hydrazone groups as binding sites.

Tris-hydrazone (1) functioned as a colorimetric chemosensor for a variety of anions such as F(-), AcO(-) and H(2)PO(4)(-). The anion binding could be easily detected by naked-eye according to color changes. The high binding ability of the receptor 1 to anions was further investigated by UV-vis absorption spectroscopy in DMSO. The results of job plot of the receptor 1 with different anions demonstrated that the stoichiometry of the complex between 1 and F(-) was 1:1 (1:anion) and the stoichiometry of the other complexes studied was 1:3 (1:anion).

Rational design of novel benzimidazole-based sensor molecules that display positive and negative fluorescence responses to anions.

Two novel and neutral benzimidazole derivatives-based anion receptors bearing a 1,10-phenanthroline fluorophore, N,N'-di-(2'-benzimidazolyl-methylene)-1, 10-phenanthroline-2,9-diamide (1) and N,N'-di-[2'-(benzimidazolyl-2'-) ethyl-]-1,10-phenanthroline-2,9-diamide (2), which exhibited turn-on and turn-off fluorescence responses to various anions, were rationally designed and synthesized and their fluorescent response toward anions was investigated in DMSO solution. In the process of anions binding, there were two different fluorescent responses in presence of anions: a quenching of the fluorescence emission for F- and AcO- and an enhancement of the fluorescence emission for Cl-, Br- and I-. Two different luminescent mechanisms of the receptors 1 and 2 resulting from various anions were exploited to rationalize quenching and enhancement of the fluorescence emission: a photo-induced electronic transfer mechanism (PET) and the increase of the rigidity of the host molecules, respectively. In particular, chloride could be recognized selectively from the anions tested according to changes of fluorescence spectrum.

A highly selective naked-eye colorimetric sensor for acetate ion based on 1,10-phenanthroline-2,9-dicarboxyaldehyde-di-(p-substitutedphenyl-hydrazone).

A new and simple colorimetric sensor with high selectivity for acetate ion based on 1,10-phenanthroline-2,9-dicarboxyaldehyde-di-(p-substitutedphenylhydrazone) receptor 2 has been synthesized. The selectively binding ability of receptor 2 to acetate ion over other anions tested was demonstrated by UV-vis absorption spectroscopy in DMSO. Comparing with other anions studied, the UV-vis absorption spectrum in dimethyl sulfoxide shows significant response toward acetate ion with high selectivity, and meanwhile dramatic color change is observed from yellow to green in the presence of acetate ion (5 x 10(-6)mol/L). Little UV-vis absorption spectrum change has occurred when receptor 2 was titrated with other different guest (F(-), Cl(-), Br(-), I(-), H(2)PO(4)(-) and OH(-)). In addition, the (1)H NMR spectrum titration shows deprotonation of the receptor in the presence of acetate ion.